The overall aim of this proposal is to examine how the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) interact in spontaneously hypertensive rats (SHR). To gain an understanding of these interactions, anesthetic agents, vasoactive substances and physiological maneuvers will be performed to alter blood pressure from the awake state and hormonal and physiological measurements made. The role of the RAS in blood pressure control in SHR will be investigated by measuring angiotensin peptides in cerebrospinal fluid and perpheral blood using radioimmunoassay and HPLC techniques. These measurements will be made awake and then after alteration of blood pressure by one of five anesthetic agents, sodium nitroprusside or hemorrhage. The contribution of the RAS to blood pressure will further be defined through central and peripheral administration of inhibitors of the renin-angiotensin system. Concentration of saralasin or MK-422, known not to alter blood pressure when given systemically, will be administered centrally. Angiotensin II will then be given to see if the effects of saralasin or MK-422 can be reversed. The SNS will be investigated in SHR through alteration in norepinephrine and serotonin before and after anesthesia. Peripheral sympathetic activity will be assessed through plasma catecholamines. Since some anesthetic agents have more profound influence on cardiac output than on peripheral resistance, the mechanism responsible for these differences will be investigated. Both norepinephrine and serotonin will be microinjected into the nucleus tractus solitarii using different anesthetic agents to assess sites of action of these anesthetics within the central nervous system. The effect of alteration in blood pressure on tissue perfusion will be investigated through the microsphere method and tissue pyruvate/lactate concentrations. The data derived from the studies will define how anesthetic agents influence the renin-angiotensin system and the sympathetic nervous system in one form of hypertension. Additional information concerning the importance of angiotensin, norepinephrine and serotonin in controlling blood pressure during anesthesia in a hypertensive model will be gained. These data will provide basic information that will aid in the development of a rational approach to the anesthetic management of hypertensive patients.